Mice injected with sublethal doses murine cytomegalovirus (MCMV) exhibit rapid and dramatic changes in their ability to generate in vitro cytotoxic T lymphocyte responses to hapten-self and to alloantigens. Within three days after intraperitoneal injection of (MCMV), the CTL responses to hapten-self and alloantigens are abrogated or severely reduced. This is followed by rapid recovery to a normal level of CTL potential, and then to a hightened state of immune potential detected by the hapten-self CTL only. The injection of F1 hybrid mice with either MCMV or parental spleen cells resulted in rapid and severe immunosuppression. Inoculation of either the virus or parental cells were selected so that they would be below the threshold for severe immunosuppression. However, when these two inocula were combined, servere immunosuppression was observed. These studies permit the investigation of the immunosuppression of MCMV infection and the possibility consequences of CMV infection coupled with a graft-versus-host reaction (GVHR).